Our Changing World: Building New Zealand’s RNA capabilities

Researchers in a laboratory wearing white lab coats and gloves examine a small vial of liquid. One person holds the vial up to eye level while another looks on. In the background, additional lab workers operate equipment near biosafety cabinets labeled “LNPs” and “RNA 2,” with benches, instruments, and pipettes visible throughout the room. — Based at the Malaghan Institute, the RNA platform lab aims to increase New Zealand’s capacity in RNA technology. Photo: Robert Cross, Image Services

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After mRNA vaccine technology burst on to the scene during the Covid-19 pandemic, the New Zealand government committed $69.5 million to increasing the country’s capacity in this area by establishing an RNA platform.

Two and a half years since establishment, Our Changing World finds out how the New Zealand RNA platform is doing, and how close we are to being able to develop our own mRNA vaccines.

A new way to make vaccines

Hantavirus and ebola are in the headlines, and flu season is upon us.

But as the Covid-19 experience showed us, we don’t always know what virus will cause the next pandemic.

Vaccines remain our greatest defence against infectious diseases.

Acting like a non-infectious trial-run, they essentially allow immune systems to prepare in advance, making them better equipped to take down an attacking virus when it shows up for real.

But getting a new vaccine to market takes time.

It needs to be researched, developed, produced and then tested in animal models. If it looks effective it must then be manufactured to a clinical grade and put through an extensive series of clinical trials to determine its safety and efficacy in humans.

For ‘traditional’ vaccines that are made using either deactivated whole viruses or virus protein parts, these steps sometimes take years or decades to work through.

A laboratory researcher uses a pipette to transfer liquid into a small plastic well plate on a bench. The workspace includes racks of tubes, a notebook with a pen, and various lab instruments. Bright overhead lighting illuminates the busy lab environment with equipment and containers arranged behind the work area. — Joanna Kuang works in the RNA production team Photo: Robert Cross

However, during the Covid-19 pandemic the Pfizer-BioNTech mRNA vaccine was made, tested and approved within 11 months across 2020. The collective efforts of scientists collaborating across the world, the large influx of research funds, overlapping clinical trials and rolling submission of data to regulators all helped, but some of this speed was due to this new way to make vaccines.

Messenger RNA (mRNA) carries instructions to protein factories in cells, directing them to make a particular protein. For a vaccine this could have the instructions for a virus protein. Instead of making the virus protein in the lab and injecting it to a person, the messenger RNA is sent to the cell’s protein factories for the virus protein to be made there.

The advantage, says Dr Lisa Connors of the Malaghan Institute of Medical Research, is that you get a much faster research process, especially when coupled with AI advances in the realm of understanding protein structures.

‘From lab to jab’

The New Zealand RNA platform is focused on seven different pillars that represent the different steps and challenges to be addressed to allow a smooth transition from an idea to a working vaccine or therapy.

As production pillar lead Dr Rebecca McKenzie explains: “Our really big goal is to build an RNA pipeline that could take a product all the way from research to the clinic”.

Rebecca is wearing a white lab coat and pink gloves, working inside a biosafety cabinet, using a pipette to dispense liquid into small tubes held in a rack. The reflective glass panel shows the workspace, which includes pipettes, tube holders, and containers organized on the stainless-steel surface. — Dr Rebecca McKenzie, RNA production team leader Photo: Robert Cross, Image Services

Rebecca’s domain is a small and extremely clean lab in the Malaghan Institute’s research space on the Victoria University of Wellington Kelburn campus.

This is where research-grade RNA products will get made on demand, quality tested, and then packaged into small bubbles of fat - which enables them to get into cells.

Before the platform was set up, researchers needed to buy RNA from companies overseas, says Rebecca. And some of these companies only produce generic RNA molecules, not the bespoke ones required to investigate new vaccines or therapies.

Since they began in late December 2023, the platform has made over 600 products, passing the 500 mark in April this year, says Rebecca,

“That was a really exciting moment and I think that represents everything we’ve done so far. So the building of the team, the lab, the methods. So those are really the hardest products to make - the first 500. And now we’re going much faster.”

There is a cost to the researchers, but in this establishment phase there’s also funding available for several projects and three ‘flagship’ projects are being used to test the steps in the pipeline from ‘lab to jab’.

One is aimed at developing a vaccine against the bacterium staphylococcus aureus, which causes a large number of infections in New Zealand. Another is targeting bovine viral diarrhoea, while the last is being run by Dr Lisa Connors and aims to develop a vaccine against any strain of influenza virus.

Influenza, which causes the flu, is very changeable. This is why the flu vaccine is different each year. The virus changes often in the area that our immune system recognises, so the vaccine needs to change too.

Two laboratory researchers in white lab coats and gloves operate a complex instrument with tubing and control dials connected to bottles. One researcher adjusts the device while another sits at a computer displaying data on a large monitor. The bench includes cables, containers, and lab equipment arranged around the system. — The RNA platform lab is designed to produce and test research grade RNA Photo: Robert Cross, Image Services

Lisa is focused on a different area of the virus, and trying to teach our immune system to recognise that instead; “There are some parts of this virus that can’t change because they’re really vital to the survival of the virus. And so we’re hunting those parts down using AI technology.”

By combining AI and mRNA advancements they’ve managed to move quickly from a huge number of vaccine candidates to a small cohort of potential vaccines that have been working well in pre-clinical lab tests says Lisa.

As well as a vaccine researcher, Lisa also leads the pre-clinical testing pillar of the RNA Platform. This involves using animal models or human cell models in the lab to test whether candidate vaccines are prompting the desired responses from immune cells.

She’s got a few more tests to go to satisfy that it works well in human cells, and for many different influenza strains, but if they go well the next step would be making clinical grade RNA and testing it in humans.

And as part of the pipeline, the team behind the RNA platform have been considering that too.

Towards vaccine production

While Rebecca leads the production team for research grade RNA, anything that is to be tested in humans requires another level of clean production, regulation and quality control.

So the platform is sharing their methods with a Timaru-based company called South Pacific Sera to enable a smooth research-grade to clinical-grade transition.

While a New Zealand company may never rival the global pharmaceutical giants, having the capability here allows research into diseases that are specific problem in this region, as well as enabling New Zealand researchers to get in the global RNA vaccine game too, says Dr Lisa Connors.

“The dream would be to make a product that a pharmaceutical company could pick up and purchase… But to get to that point, before they’re even interested in the product, you have to show that it works well”.

And with the US pulling funding for its RNA vaccine research, Lisa says it’s more important than ever that New Zealand continues building up its capacity.

Not just vaccines

While the three flagship projects for the platform are vaccine based, it’s not the only avenue being explored for this technology, says Dr Rebecca McKenzie.

Other researchers at the Malaghan Institute for Medical Research are investigating whether it can be used to help immune systems better identify cancer cells, while therapies based around shorter pieces of RNA that change gene expression in cells are already in clinical trials for disease treatment (Our Changing World reported on one such trial in 2023). And outside of human uses, RNA technology is also being researched for use in plants, animals, and insects.

A portrait of a smiling Lisa in a Malaghan Institute white lab coat stands beside a bench with an open centrifuge. The bench holds pipettes, containers, and lab supplies, with shelving and equipment visible in the background. — Dr Lisa Connor is leading a project to develop an influenza vaccine Photo: Peleg

The RNA Platform received funding for seven years. Two and a half years in, New Zealand is not quite ready yet to produce its own mRNA vaccines if a pandemic hit tomorrow, but, Rebecca says, they’re working on it:

“It’s a huge building process starting from zero and getting everyone able to do their part and get all the things co-ordinated to do that research grade, the clinical grade and make products that could go out into the clinic… So seven years is a really nice springboard to help us build the things we might need to then go further.”